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Therapeutic regulation of complement activation in extracorporeal circuits and intravascular treatments with special reference to the alternative pathway amplification loop |
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| Authors: | Kristina N Ekdahl Karin Fromell Marco Mannes Karl-Henrik Grinnemo Markus Huber-Lang Yuji Teramura Bo Nilsson |
| Institution: | 1. Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Uppsala, Sweden;2. Institute for Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany;3. Department of Surgical Sciences, Division of Cardiothoracic Surgery, Uppsala University, Uppsala University Hospital, Uppsala, Sweden;4. Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Uppsala, Sweden
Cellular and Molecular Biotechnology Research Institute (CMB), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan Master's/Doctoral Program in Life Science Innovation (T-LSI), University of Tsukuba, Tsukuba, Japan |
| Abstract: | A number of clinical treatment modalities involve contact between blood and biomaterials: these include extracorporeal circuits such as hemodialysis, cardiopulmonary bypass, plasmapheresis, and intravascular treatments. Common side effects arising from these treatments are caused by activation of the cascade systems of the blood. Many of these side effects are mediated via the complement system, including thromboinflammatory reactions and rejection of implants. Depending on the composition of the materials, complement activation is triggered via all the activation pathways but is by far mostly driven by the alternative pathway amplification loop. On biomaterial surfaces the alternative pathway amplification is totally unregulated and leads under optimal conditions to deposition of complement fragments, mostly C3b, on the surface leading to a total masking of the underlying surface. In this review, we discuss the mechanism of the complement activation, clinical consequences of the activation, and potential strategies for therapeutic regulation of the activation, using hemodialysis as demonstrator. |
| Keywords: | alternative pathway complement regulation extracorporeal treatment hemodialysis thromboinflammation |